For a virus to grow in a host, it must find a way around the immune response that it causes. One of the first lines of immune defense against viral infection is the interferon (IFN) response. The IFN response is used to signal an antiviral state in the cell that is infected and to neighboring cells. Many viruses that block the IFN response can proliferate in the host cell. Viruses can do this by producing certain products that block specific parts of the interferon pathway. Two viruses that have this function are ebola and influenza viruses. Ebola virus has viral protein 35 (VP35) which can block the IFN pathway. In preliminary data, VP35 is found to block the phosphorylation of interferon regulatory factor 3 (IRF-3) which is known to transcriptionally induce IFN genes. It is then hypothesized that VP35 interacts with a cellular protein. Similarly it has also been shown that the nonstructural protein 1 (NS 1) of influenza virus can block IRF-3 activation. Also there is a host specie-specificity for NS 1, implying that there should be an interaction with a cellular protein. This proposal outlines the identification and characterization of the cellular proteins that VP35 and NS 1 interacts with.